E1B缺失腺病毒瘤内注射治疗恶性肿瘤的安全性研究

背景及目的:具有复制能力的病毒(或称溶瘤病毒)用于治疗恶性肿瘤的研究近年来发展相当迅速,E1B缺失腺病毒是目前研究最多、进展最快的溶瘤病毒之一。本研究目的是观察瘤内注射E1B缺失腺病毒注射液(H101)治疗恶性肿瘤的安全性。方法:按入选标准筛选肿瘤患者15例,给予H101瘤内注射,注射剂量在每人每天5×107～1.5×1012颗粒数,采用5个剂量级进行爬升,连续5天为一疗程。治疗前对患者进行全面体检,治疗期间密切观察患者的生命体征和不良反应,治疗后不同时间采集患者的血、尿、咽拭子及注射部位拭子进行腺病毒DNA测定(PCR法)。结果:15例患者均可进行毒性评价。所有患者对H101瘤内注射耐受性良好,在整个治疗过程中,没有观察到剂量限制性毒性(DLT),也未见严重不良事件,主要不良反应为注射局部疼痛(60.0%)和发热(33.3%)。血、尿、咽拭子及注射部位拭子中均未检测到腺病毒DNA。结论:E1B缺失腺病毒注射液(H101)瘤内注射毒副作用较低,患者耐受性良好,也未发现H101向体外播散的证据。因此,H101瘤内注射具有良好的安全性。

Safety of an E1B deleted adenovirus administered intratumorally to patients with cancer

BACKGROUND & OBJECTIVE: In recent years, great development has been made in cancer therapeutics with replication-competent viruses (oncolytic viruses). Genetically modified adenovirus is one of promising viruses. The current study was designed to evaluate the safety of intratumoral H101, an E1B deleted adenovirus. METHODS: A total of 15 patients with malignant tumors were treated with H101 in a dose-escalation manner (from 5 x 10(7) VP to 1.5 x 10(12) VP per day for 5 consecutive days). Systemic examination was performed prior to injection. Physical signs (including weight, temperature, respiration,pulse, and blood pressure) and toxicity were observed and recorded carefully during treatment. Adenoviral DNA in plasma, urine, and swabs of oropharynx, swabs of the injection site from different time-point were determined by PCR. RESULTS: Evaluation of toxicity in all 15 cases was available. All patients tolerated well following intratumoral injection of H101. Dose limited toxicity (DLT) and serious adverse event (SAE) were not found in the course of treatment. Main side effects were injection site pain (60.0%) and fever (33.3%). Adenoviral DNA was undetectable in plasma, urine, and swabs of oropharynx, swabs of the injection site. CONCLUSION: This study showed that the toxicities of intratumoral injection of E1B deleted adenovirus (H101) were lower and tolerable. There is no evidence indicating the invasion. These results suggested that intratumorally injected H101 is safe.